The herpesviruses are the largest and most complex of the known oncogenic DNA viruses and are suspected of playing some role in the development of cervical carcinoma, Burkitt's lymphoma, nasopharyngeal carcinoma and Kaposi's sarcoma. They are also of major concern as reactivated infections and potential tumorigenic agents in immunosuppressed patients. Our research focuses on aspects of herpesviruses molecular biology centering around interactions between viral DNA and cellular DNA and including the mechanism of morphological transformation. We include in this category studies on focus formation with isolated and cloned viral DNA fragments, studies on the mechanism of HSV thymidine kinase mediated gene transfer and analysis of the complications caused by cell-virus homology in DNA and RNA hybridization studies. These experiments should provide the background knowledge, insight and experience that will be necessary for proper evaluation of the significance of herpesvirus DNA sequences found in human tissue and tumor samples. Current projects include: (1) Examination of the mechanism of transformation by the cloned HSV-2 BglII-N sequence, including construction of insertion mutations and attempts to enhance transformation efficiency by linkage to LTR sequences and other strong viral promoters; (2) Attempts to identify the gene in DNA-fragment transformed cells that confers focus formation ability to NIH/3T3 cells and a search for sequences with "enhancer" or "insertion element" properties within Bg1II-N; (3) Attempts to construct coselected cell lines expressing the major DNA binding protein and 140K/38K complex that have been associated with cerival carcinoma cells by immunological or serological studies; (4) further study of the mechanism of specific loss of part of the Bg1II DNA in LTK+ coselected cell lines; (5) Detailing mapping of the structure of the integrated TK-IFN hybrid gene in LH2pl92-8 cells which express interferon only after viral superinfection; and (6) Isolation and structural analysis of cloned HSV-DNA sequences from human tumor DNA.